chr7-93450315-T-C

Variant names:

• chr7-93450315-T-C
• rs6465381
• NM_001742.4:c.649-6558A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001742.4(CALCR):​c.649-6558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,922 control chromosomes in the GnomAD database, including 1,735 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1735 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 4 publications found

Genes affected

CALCR (HGNC:1440): (calcitonin receptor) This gene encodes a high affinity receptor for the peptide hormone calcitonin and belongs to a subfamily of seven transmembrane-spanning G protein-coupled receptors. The encoded protein is involved in maintaining calcium homeostasis and in regulating osteoclast-mediated bone resorption. Polymorphisms in this gene have been associated with variations in bone mineral density and onset of osteoporosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

CALCR Gene-Disease associations (from GenCC):

• osteoporosis

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.649-6558A>G		intron_variant	Intron 8 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.697-6558A>G		intron_variant	Intron 10 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.649-6558A>G		intron_variant	Intron 7 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.649-6558A>G		intron_variant	Intron 8 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21545 AN: 151806 Hom.: 1733 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21564 AN: 151922 Hom.: 1735 Cov.: 32 AF XY: 0.142 AC XY: 10567 AN XY: 74250

African (AFR) AF: 0.131 AC: 5432 AN: 41478

American (AMR) AF: 0.0910 AC: 1386 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3468

East Asian (EAS) AF: 0.105 AC: 540 AN: 5142

South Asian (SAS) AF: 0.0712 AC: 343 AN: 4818

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10560

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10405 AN: 67908

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.141 Hom.: 2915

Bravo AF: 0.130

Asia WGS AF: 0.0960 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.72
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6465381; hg19: chr7-93079627;